This is a resubmission application for a Competing Renewal of a currently funded grant (R01-DA13165-10). The overall aim of this project is to investigate the psychological and neural basis of human cognitive control in healthy adults. Since the last competing review of this project, we have published 19 refereed publications that have elucidated the mechanisms of cognitive control in attention shifting and task switching using functional magnetic resonance imaging (fMRI) and suitably designed behavioral paradigms. Successful cognitive control requires both stability (maintained states of attention and memory despite distraction) and flexibility (to rapidly reconfigure attention and cognition in light of ongoing events). The proposed project will further explore these issues using novel methods and with a focus on both cortical and subcortical brain mechanisms. Aim 1 investigates purely voluntary acts of control-that is, task switching that is not prompted by a cue, but instead results from a purely voluntary decision. We will use a novel multivariate pattern analysis method we have developed (Multivoxel Pattern Time Course or MVPtc) that dynamically tracks multivoxel patterns of brain activity-and the corresponding states of attention or task engagement they engender-as these states unfold over time. This method permits us to relate brain activity with patterns of behavioral performance, as well as to explore functional connectivity within brain circuits that are associated with these cognitive states. In Aim 2 we examine the role of the basal ganglia in cognitive flexibility and stability during task switching, using both BOLD fMRI and PET dopamine imaging. We will elaborate upon recent evidence for the role of the basal ganglia- and specifically the dopamine system-in nonmotoric acts of cognitive control. Finally, in Aim 3, we will examine failures of cognitive control when distracting stimuli impair perceptual performance, with a particular emphasis on the role of experienced value and reward history on the degree to which a stimulus may capture attention. Using MVPtc, we will track fluctuations in the susceptibility to distraction by salient perceptual events or by stimuli previously associated with reward, and we will measure the degree to which top-down control can modulate attentional capture. Finally, we will use parallel PET dopamine imaging and BOLD fMRI to measure changes in striatal dopamine release evoked by salient or high-value stimuli, and correlate this with behavioral measures of distraction. Together these experiments will provide new insights about the brain mechanisms of cognitive control, a core human mental faculty that is subject to debilitating impairment due to afflictions such as drug and alcohol addiction, schizophrenia, Parkinson's and Huntington's Disease, OCD, and attention deficit hyperactivity disorder. This project will contribute to the basic-research foundation for clinical research into the causes and treatment of executive function impairments. PUBLIC HEALTH RELEVANCE: The proposed project investigates the psychological and brain bases of cognitive control-that is, goal-directed, intentional behavior, such as shifting attention or switching between tasks-as well as failures of cognitive control (including perseveration, cognitive lapses, and distraction). Executive control of cognitive function is a core human mental faculty that is subject to debilitating impairment due to afflictions such as drug and alcohol addiction, schizophrenia, Parkinson's and Huntington's Disease, attention deficit hyperactivity disorder, post traumatic stress disorder, or brain damage following stroke. This project will contribute to the basic-research foundations for clinical research into the causes and treatment of executive function impairments.